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Effect of intravenous ghrelin administration, combined with alcohol, on circulating metabolome in heavy drinking individuals with alcohol use disorder
Author(s) -
Kärkkäinen Olli,
Farokhnia Mehdi,
Klåvus Anton,
Auriola Seppo,
Lehtonen Marko,
Deschaine Sara L.,
Piacentino Daria,
Abshire Kelly M.,
Jackson Shelley N.,
Leggio Lorenzo
Publication year - 2021
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.14719
Subject(s) - ghrelin , metabolite , placebo , medicine , endocrinology , alcohol , alcohol use disorder , pharmacology , hormone , chemistry , biochemistry , alternative medicine , pathology
Background Ghrelin may influence several alcohol‐related behaviors in animals and humans by modulating central and/or peripheral biological pathways. The aim of this exploratory analysis was to investigate associations between ghrelin administration and the human circulating metabolome during alcohol exposure in nontreatment seeking, heavy drinking individuals with alcohol use disorder (AUD). Methods We used serum samples from a randomized, crossover, double‐blind, placebo‐controlled human laboratory study with intravenous (IV) ghrelin or placebo infusion in two experiments. During each session, participants received a loading dose (3 µ g/kg) followed by continuous infusion (16.9 ng/kg/min) of acyl ghrelin or placebo. The first experiment included an IV alcohol self‐administration (IV‐ASA) session and the second experiment included an IV alcohol clamp (IV‐AC) session, both with the counterbalanced infusion of ghrelin or placebo. Serum metabolite profiles were analyzed from repeated blood samples collected during each session. Results In both experiments, ghrelin infusion was associated with an altered serum metabolite profile, including significantly increased levels of cortisol (IV‐ASA q ‐value = 0.0003 and IV‐AC q < 0.0001), corticosterone (IV‐ASA q = 0.0202 and IV‐AC q < 0.0001), and glycochenodeoxycholic acid (IV‐ASA q = 0.0375 and IV‐AC q = 0.0013). In the IV‐ASA experiment, ghrelin infusion increased levels of cortisone ( q = 0.0352) and fatty acids 18:1 ( q = 0.0406) and 18:3 ( q = 0.0320). Moreover, in the IV‐AC experiment, ghrelin infusion significantly increased levels of glycocholic acid ( q < 0.0001) and phenylalanine ( q = 0.0458). Conclusion IV ghrelin infusion, combined with IV alcohol administration, was associated with increases in the circulating metabolite levels of corticosteroids and glycine‐conjugated bile acids, among other changes. Further research is needed to understand the role that metabolomic changes play in the complex interaction between ghrelin and alcohol.